A Bioinformatic Analysis of Arginine-Sensitive Regulation of rat Hepatic Gene Expression

Goals of the Study: 1. Assess the scope of arginine-responsive hepatic gene expression using in vitro rat models. 2. Compare normal and tumorigenic cells 3. Identify potentially novel genes and pathways that may be subject to amino acid (arginine) regulation Background: We previously reported that mRNA levels of the tumor associated glycoprotein amino acid transporter TA1/LAT1/ CD98 light chain arginine increase in normal hepatic cells under low arginine conditions while levels are constitutive and high in hepatic tumor cells. This suggested LAT1 amino acid response was associated with the normal hepatic phenotype and lost in carcinogenesis and may impact cell growth and survival in the tumor microenvironment. We sought to investigate how many and what types of genes are responsive to a change in arginine levels over 18 hrs using an in vitro model system. Experimental design: Differential gene expression was determined by microarrays using samples from triplicates of normal and transformed cells subjected to 18 hour arginine-deprivation compared to controls Keywords = arginine Keywords = hepatocyte Keywords = cancer Keywords = rat Keywords = amino acid Keywords = gene regulation Keywords = microarray Keywords: repeat sample